title: Galectin-4 Reduces Migration and Metastasis Formation of Pancreatic Cancer Cells.
abstract: Galectin-4 (Gal-4) is a member of the galectin family of glycan binding proteins that shows a significantly higher expression in cystic tumors of the human pancreas and in pancreatic adenocarcinomas compared to normal pancreas. However, the putative function of Gal-4 in tumor progression of pancreatic cancer is still incompletely understood. In this study the role of Gal-4 in cancer progression was investigated, using a set of defined pancreatic cancer cell lines, Pa-Tu-8988S (PaTu-S) and Pa-Tu-8988T (PaTu-T), as a model. These two cell lines are derived from the same liver metastasis of a human primary pancreatic adenocarcinoma, but differ in their growth characteristics and metastatic capacity. We demonstrated that Gal-4 expression is high in PaTu-S, which shows poor migratory properties, whereas much lower Gal-4 levels are observed in the highly metastatic cell line PaTu-T. In PaTu-S, Gal-4 is found in the cytoplasm, but it is also secreted and accumulates at the membrane at sites of contact with neighboring cells. Moreover, we show that Gal-4 inhibits metastasis formation by delaying migration of pancreatic cancer cells in vitro using a scratch assay, and in vivo using zebrafish (Danio rerio) as an experimental model. Our data suggest that Gal-4 may act at the cell-surface of PaTu-S as an adhesion molecule to prevent release of the tumor cells, but has in addition a cytosolic function by inhibiting migration via a yet unknown mechanism.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Belo
authors.forename: Astrid M
authors.initials: AM
authors.lastname: van der Sar
authors.forename: Boris
authors.initials: B
authors.lastname: Tefsen
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D037541:Galectin 4 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D037541:Galectin 4; D012333:RNA, Messenger